泌尿科PU, YEONG-SHIAUYEONG-SHIAUPUCHEN, JUNJUNCHENHUANG, CHAO-YUANCHAO-YUANHUANG2009-01-162018-07-112009-01-162018-07-112002http://ntur.lib.ntu.edu.tw//handle/246246/97138Objectives. To explore the therapeutic efficacy of arsenic trioxide (AS(2 )O(3)) in human transitional cell carcinomas, we investigated the potential use of the compound as a chemotherapeutic agent and the possible cross-resistance with cisplatin in this malignancy. Methods. Three bladder transitional carcinoma cell lines, NTUB1, NTUB1/P (cisplatin - resistant), and NTUB1/As (AS(2)O(3)-resistant), were used. The chemosensitivity of the three cell lines to cisplatin and AS(2)O(3) was determined by the microculture tetrazolium assay. The modulatory effect of buthionine sulfoximine (BSO ) on AS(2)O(3) cytotoxicity was studied by combining the two agents simultaneously or sequentially and evaluated using the median-effect analysis. Cellular glutathione contents were determined using a biochemical method. Results. There was evident cross- resistance between cisplatin and AS(2)O(3) in the cell model used. BSO significantly enhanced AS(2)O(3 ) cytotoxicity in the three cell lines, indicating synergism in combination. In the presence of 3 muM BSO, the sensitivity of NTUB1, NTUB1/P, and NTUB1/As to AS(2)O(3) was increased 3, 7.4, and 8.4-fold, respectively. Among the three different combination schedules, greater cytotoxic effects were obtained by concurrent exposure to both agents. A significant dose-response relationship was found between the BSO concentrations and glutathione contents in NTUB1 (P= 0.007) and NTUB1/As (P = 0.05) but not NTUB1/P (P = 0.1) cells. Conclusions. AS(2)O(3 ) in the presence of BSO may be an active agent against transitional cell carcinoma. Our results have clinical implications and warrant further investigation. (C) 2002, Elsevier Science Inc.en-USACUTE PROMYELOCYTIC LEUKEMIANF-KAPPA-BGROWTH-INHIBITIONCANCER-CELLSIN-VITROAPOPTOSIS[SDGs]SDG3